Heterogeneous blood-tumor barrier permeability determines drug efficacy in experimental brain metastases of breast cancer.

Purpose: Brain metastases of breast cancer appear to be increasing in incidence, confer significant morbidity, and threaten to compromise gains made in systemic chemotherapy. The blood-tumor barrier (BTB) is compromised in many brain metastases; however, the extent to which this influences chemotherapeutic delivery and efficacy is unknown. Herein, we answer this question by measuring BTB passive integrity, chemotherapeutic drug uptake, and anticancer efficacy in vivo in two breast cancer models that metastasize preferentially to brain.

Vorinostat inhibits brain metastatic colonization in a model of triple-negative breast cancer and induces DNA double-strand breaks.

Purpose: As chemotherapy and molecular therapy improve the systemic survival of breast cancer patients, the incidence of brain metastases increases. Few therapeutic strategies exist for the treatment of brain metastases because the blood-brain barrier severely limits drug access. We report the pharmacokinetic, efficacy, and mechanism of action studies for the histone deactylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in a preclinical model of brain metastasis of triple-negative breast cancer.

Uptake of ANG1005, a novel paclitaxel derivative, through the blood-brain barrier into brain and experimental brain metastases of breast cancer.

Purpose: We evaluated the uptake of angiopep-2 paclitaxel conjugate, ANG1005, into brain and brain metastases of breast cancer in rodents. Most anticancer drugs show poor delivery to brain tumors due to limited transport across the blood-brain barrier (BBB). To overcome this, a 19-amino acid peptide (angiopep-2) was developed that binds to low density lipoprotein receptor-related protein (LRP) receptors at the BBB and has the potential to deliver drugs to brain by receptor-mediated transport.

Using WebCt to implement a basic science competency education course.

Objective: To implement a model of competency-based education in a basic science competency course using WebCT to improve doctor of pharmacy (PharmD) students' understanding and long-term retention of course materials.

Methods: An anatomy-cell biology course was broken down into 23 modules, and worksheets and mirrored examinations were created for each module. Students were allowed to take the proctored examinations using WebCT as many times as they wanted, with each subsequent test containing a new random subset of questions.

Brain iron toxicity: differential responses of astrocytes, neurons, and endothelial cells.

Iron accumulation or iron overload in brain is commonly associated with neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, and also plays a role in cellular damage following hemorrhagic stroke and traumatic brain injury. Despite the brain's highly regulated system for iron utilization and metabolism, these disorders often present following disruptions within iron metabolic pathways. Such dysregulation allows saturation of proteins involved in iron transport and storage, and may cause an increase in free ferrous iron within brain leading to oxidative damage.

Voltage-gated calcium channels provide an alternate route for iron uptake in neuronal cell cultures.

Recent studies suggest that iron enters cardiomyocytes via the L-type voltage-gated calcium channel (VGCC). The neuronal VGCC may also provide iron entry. As with calcium, extraneous iron is associated with the pathology and progression of neurodegenerative diseases such as Parkinson's and Alzheimer's disease.

Hepatocyte growth factor-regulated genes in differentiated RAW 264.7 osteoclast and undifferentiated cells.

Hepatocyte Growth Factor (HGF) and its protooncogene receptor c-Met regulate osteoclast function by activating pp60(c-Src) kinase and alpha(v)beta3 integrin. HGF causes transcription yet in osteoclast cells, this gene regulation is currently unknown. To begin characterization of HGF-regulated gene expression in osteoclast cells, we used a well characterized model of osteoclast cells.